Relevance of 2'-O-Methylation and Pseudouridylation for the Malignant Melanoma.

Simon Jasinski-Bergner,Barbara Seliger,Juliane Blümke,Claudia Wickenhauser

doi:10.3390/cancers13051167

Abstract

Simple SummaryThis study investigates the expression, the histological localization, and the influence of the factors involved in 2′-O-methylation and pseudouridylation on prognostic relevant markers, proliferation markers, overall survival, molecular immune surveillance and evasion mechanisms within the malignant melanoma. Statistically significant positive correlations to the expression of markers involved in cell proliferation were observed. The upregulation of the RNA modifying factors was of prognostic relevance in this tumor disease with a negative impact on the overall survival of melanoma patients. Furthermore, the factors involved in 2′-O-methylation and pseudouridylation were statistically significant negative correlated to the expression of human leukocyte antigen class I genes as well as of components of the antigen processing machinery.The two RNA modifications 2′-O-methylation and pseudouridylation occur on several RNA species including ribosomal RNAs leading to an increased translation as well as cell proliferation associated with distinct functions. Using malignant melanoma (MM) as a model system the proteins mediating these RNA modifications were for the first time analyzed by different bioinformatics tools and public available databases regarding their expression and histological localization. Next to this, the impact of these RNA-modifying factors on prognostic relevant processes and marker genes of malignant melanoma was investigated and correlated to immune surveillance and evasion strategies. The RNA modifying factors exerted statistically significant positive correlations to the expression of genes involved in cell proliferation and were statistically significant negative correlated to the expression of human leukocyte antigen class I genes as well as of components of the antigen processing machinery in malignant melanoma. Upregulation of the RNA modifying proteins was of prognostic relevance in this tumor disease with a negative impact on the overall survival of melanoma patients. Furthermore, the expression of known oncogenic miRs, which are induced in malignant melanoma, directly correlated to the expression of factors involved in these two RNA modifications.

Highlights

Malignant melanoma (MM) refers to a neoplasm of melanocytes comprising of neural crest-derived cells located in particular in the stratum basal of the skin’s epidermis and in the uvea of the eye
Melanocytes are not linked to the basal lamina by hemidesmosomes and do not have desmosomes to neighboring keratinocytes
UV light exposition leading to DNA damages and oxidative stress in melanocytes [4], nevus number, pigmentation characteristics as well as genetic mutations are known predispositions for the processes leading to malignant transformation [5]

Summary

Introduction

Malignant melanoma (MM) refers to a neoplasm of melanocytes comprising of neural crest-derived cells located in particular in the stratum basal of the skin’s epidermis and in the uvea of the eye. Melanocytes as well as adjacent keratinocytes express, e.g., E-cadherin on their cell surface [1], which is an important factor contributing to the cell migration and invasion of melanoma cells after malignant transformation of melanocytes. Due to this migratory ability, growth characteristics as well as other properties including resistance to radiation and certain chemotherapeutics [2], MM represents the deadliest type of skin cancer with increasing incidences [3]. Concerning the hereditary predisposition, it is known that between 5–10% of melanoma cases are familial [6] and mainly induced by germ line mutations in tumor suppressor genes involved in proliferation control and DNA repair of cells

Results

Discussion

Conclusion